Pharmacokinetics and Pharmacodynamics

Abstract

The theoretical background provided by L. E. Mather and G. K. Gourlay (this volume) indicated that the TTS fentanyl systems can provide a zero order input rate for at least 24 h that would mimic a constant rate intravenous infusion. In fact, the TTS fentanyl systems at a delivery rate of 100 µg/h have been shown to provide similar serum fentanyl concentrations at steady state to the intravenous infusion of fentanyl at an equivalent rate [6]. The currently available methods of treating postoperative pain have also been reviewed (Part 2). The continuous infusion of a number of opioids including morphine [18], pethidine [19] and fentanyl [14] has been shown to provide more reliable postoperative pain relief than that obtained from conventional intramuscular opioid regimens. However, there is at least a five-fold range of interpatient variability in the minimum effective blood opioid concentration (MEC) required to effectively control postoperative pain [2, 5, 8, 20]. Therefore, there are at least two possible approaches in the clinical implementation of zero order infusions to control postoperative pain. Firstly, the physician could use infusion rates which will provide steady-state blood opioid concentrations that are towards the higher end of the range of MECs, thereby providing acceptable pain relief to the majority of patients. The disadvantage of the approach is that the steady-state concentrations will still be inadequate for some patients while being excessive for a significant proportion of patients, probably causing unwanted and unpleasant side effects.The second approach is to attempt to individualize the infusion rate for each patient to maximize pain relief but minimize side effects.